DNA Enhancer Looping and the Logic of Gene Regulation
Faculty Mentor Information
Matthew L. Ferguson
Presentation Date
7-2017
Abstract
Biotechnical advancements during the past few years have led to an explosion of information available on eukaryotic gene regulation. Eukaryotic cells change which genes are expressed by the contact of a ‘gene activator region’ called an ‘enhancer’ to another region termed ‘promoter’ which recruits RNA polymerase to begin the transcription process. These regions are in many cases kilobase distance from each other; presenting an action-at-a-distance problem. We embrace a popular model which solves this distance problem through 3-dimensional ‘looping’ of the DNA. A recent kilobase-resolution Hi-C (Genome Conformation Capture) (Rao et al. 2014; Sanborn et al. 2015) experiment appears to have confirmed that the well-studied Beta-Globin locus is governed by a two-loop enhancer and promoter system. We show that the Beta-Globin locus and other gene loci like it can be understood to operate according to boolean logic. Using boolean algebra, propositional logic, and principles of logic circuits, we understand DNA enhancer looping as a digital logic gate network. Evaluating genes as circuits in this way takes us closer to genomic engineering and deeper understanding. This project represents an essential step toward further clarifying the organization of the genome and epigenetic regulation.
DNA Enhancer Looping and the Logic of Gene Regulation
Biotechnical advancements during the past few years have led to an explosion of information available on eukaryotic gene regulation. Eukaryotic cells change which genes are expressed by the contact of a ‘gene activator region’ called an ‘enhancer’ to another region termed ‘promoter’ which recruits RNA polymerase to begin the transcription process. These regions are in many cases kilobase distance from each other; presenting an action-at-a-distance problem. We embrace a popular model which solves this distance problem through 3-dimensional ‘looping’ of the DNA. A recent kilobase-resolution Hi-C (Genome Conformation Capture) (Rao et al. 2014; Sanborn et al. 2015) experiment appears to have confirmed that the well-studied Beta-Globin locus is governed by a two-loop enhancer and promoter system. We show that the Beta-Globin locus and other gene loci like it can be understood to operate according to boolean logic. Using boolean algebra, propositional logic, and principles of logic circuits, we understand DNA enhancer looping as a digital logic gate network. Evaluating genes as circuits in this way takes us closer to genomic engineering and deeper understanding. This project represents an essential step toward further clarifying the organization of the genome and epigenetic regulation.